Specific cell surface receptors for both transferrin, the iron transport protein, and transcobalamin II, the cobalamin (vitamin B12) transport protein, have been found in a number of cells or tissues including red blood cell precursors, liver, placenta, diploid fibroblasts in culture, and some neoplastic cell lines. In the past two years, I have purified to homogeneity both the transferrin and transcobalamin II receptors from human placenta. The purified receptor proteins and specific antibodies raised against both of these proteins will be utilized to study the mechanism of binding, uptake, and release of iron and cobalamin in different cells and tissues. The development of radioimmunoassays for receptor proteins will be utilized to study regulation of receptors by different cells and tissues under various conditions. Receptors will be studied from tissues obtained from patients with congenital abnormalities of iron and cobalamin transport including hemochromatosis and transcobalamin II deficiency. Experiments will also be performed on receptors from different tumor systems. Results of these studies could lead to a better understanding of iron and cobalamin in normal and pathologic conditions, may better elucidate the biochemical defects responsible for hemochromatosis and transcobalamin II deficiency, and may advance the knowledge of membrane receptor metabolism and regulation in general.